Ingestion and killing of bacteria by polymorphonuclear neutrophils is an important part of the normal host defense against bacterial infection. The principal investigator plans to continue studies concerning normal mechanisms as well as studies on derangements of PMN bactericidal activity. Certain virulent bacteria resist killing by PMN. We plan to study the interaction of PMN and virulent Salmonella typhi. Preliminary work suggests that virulent strains of this organism fail to trigger oxidative metabolism after being ingested by PMN. Gonococci have the ability to stick to many surfaces including external membranes of the PMN. The effect of membrane adherence versus ingestion will be studied. Thus, we should clarify the role of various types of bacterial-PMN interaction on stimulation of periphagocytic events such as oxygen consumption, hexose monophosphate shunt activity, degranulation, and bactericidal activity. Certain strains of Streptococcus pyogenes have the ability to rapidly destroy PMN which they come in contact with. We are investigating this interaction with special attention to the events inside the PMN. Morphological and biochemical data suggest that PMN granules fire their enzymes into the cytoplasm and this may be part of the mechanisms of the destruction of the PMN. We are investigating modulators of this interaction in hopes of better understanding of this phenomenon.